Hydrochloric Acid → 4-(4-Pyrimidinyl)benzoyl chloride

HRID 586207Notes

Reaction equation

HRID 586207 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:16]=[CH:15][C:10]([C:11](OC)=[O:12])=[CH:9][CH:8]=2)=[N:3][CH:2]=1.[OH-].[Na+].[ClH:19]>C(O)C>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([Cl:19])=[O:12])=[CH:9][CH:8]=2)=[N:3][CH:2]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 22329706HCID 22329706, compound

Product 1

HCID 223297424-(4-Pyrimidinyl)benzoyl chloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Methyl 4-(4-pyrimidinyl)benzoate (0.41 g, 1.9 mmol) was stirred at room temperature in ethanol (20 mL) and 2N NaOH(aq) (20 mL) for 1 hour. 2N HCl(aq) was added until a precipitate formed. The resulting suspension was concentrated in vacuo and azeotroped with toluene. Thionyl chloride (100 mL) and DMF (1 drop) were added and the reaction mixture refluxed for 1 hour. The reaction mixture was concentrated in vacuo and azeotroped twice with dichloromethane to yield 4-(4-pyrimidinyl)benzoyl chloride. The acid chloride was suspended in dichloromethane (100 mL) and 1-(6-bromonaphth-2-ylsulphonyl)piperazine hydrochloride (0.545 g, 1.5 mmol) added as a solid in two portions followed by triethylamine (2.2 mL, 15 mmol). The reaction mixture was stirred overnight at room temperature then concentrated in vacuo. The resulting solid was separated between ethyl acetate (100 mL) and water (2×100 mL). The organic layer was dried over magnesium sulphate, filtered and concentrated in vacuo to yield a black oil which was subjected to chromatography (SiO2: 40%, 50%, 60% Ethyl acetate/Hexane) to yield 1(6-bromonaphth-2-ylsulphonyl)4-[4-(4-pyrimidinyl)benzoyl]piperazine as a white solid; 1H NMR (250 MHz, DMSO-d6) δ=2.94 to 3.18 ppm (m,4H), δ=3.40 to 3.83 ppm (m,4H), δ=7.49 ppm (d,2H), δ=7.83 ppm (m,2H), δ=8.10 ppm (dd,1H), δ=8.14 to 8.23 ppm (m,4H), δ=8.43 ppm (d,1H), δ=8.49 ppm (s,1H), δ=8.89 ppm (d,1H), δ=9.26 ppm (s,1H); MS (M+H)+ 536.

Workup

  1. customformed
  2. concentrationThe resulting suspension was concentrated in vacuo
  3. customazeotroped with toluene
  4. additionThionyl chloride (100 mL) and DMF (1 drop) were added
  5. temperaturethe reaction mixture refluxed for 1 hour
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. customazeotroped twice with dichloromethane

Sources & evidence

ORD record
ord-16c622f227ef4e92b374826168922897
Source dataset
uspto-grants-2005_08
Patent number
US06936610B2

Reaction notes

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